New Potent SARS-CoV 3C-Like Protease Inhibitors Derived from Thieno[2,3-d]pyrimidine Derivatives

2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1) condensed with carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines (4a,b). Compound 4a condensed with acetophenone under Vilsmeier conditions to afford the formylated pyrazolopyrimidine 6. Condensation of 4a with active methylenes produced the respective pyrazolopyrimidines (7-11). Besides, 4a condensed with succinic anhydride and with phthalic anhydride, yielding the pyrrolidine-2,5-dione 12 and the isoindoline-1,3-dione 13, respectively. Moreover, 4a reacted with isatin to afford the hydrazono-indolin-2-one 14. Structural elucidations for the new thienopyrimidines were based upon compatible analytical and spectroscopic results. Eleven of the new compounds were tested and found active against influenza A neuraminidase virus (H3N2). Compounds 12 and 13 were the most potent.